A New Pyridazine Series of GABAA α5 Ligands

Van Niel, M.B.; Wilson, K.; Adkins, C.H.; Atack, J.R.; Castro, J.L.; Clarke, D.E.; Fletcher, S.; Gerhard, U.; Mackey, M.M.; Malpas, S.; Maubach, K.; Newman, R.; O'Connor, D.; Pillai, G.V.; Simpson, P.B.; Thomas, S.R.; MacLeod, A.M.

Author

Van Niel, M.B.

Wilson, K.

Adkins, C.H.

Atack, J.R.

Castro, J.L.

Clarke, D.E.

Fletcher, S.

Gerhard, U.

Mackey, M.M.

Malpas, S.

Maubach, K.

Newman, R.

O'Connor, D.

Pillai, G.V.

Simpson, P.B.

Thomas, S.R.

MacLeod, A.M.

Abstract

Screening of the Merck compound collection identified 6 as an unusually simple, low molecular weight hit with moderate affinity for GABAA receptors. The structural novelty of 6, compared to our advanced series of GABAA α5 inverse agonists, made it an attractive molecule for further exploration. This paper will describe the evolution of 6 into a new series of ligands with nanomolar affinity and functional selectivity for GABAA α5 receptor subtypes.